The TRH-like peptides pGlu-Glu-Pro amide, pGlu-Phe-Pro amide, and pGlu-Gln-Pro amide were isolated and identified some years ago, and these peptides have been proven to be present in many tissues and fluids. The presence of TRH-like immunoreactivity distinct from TRH in blood has been observed previously. In the present study, the presence of N-extended forms of TRH-like peptides in plasma has been investigated. Peripheral blood samples of human, rat, and rabbit were obtained and plasma was extracted. The peptides were separated in several steps of chromatography, including gel filtration, cation and anion exchange, and HPLC. The concentrations of the TRH-like peptides in the column fractions were measured by RIA with TRH antibody. The N-extended forms of TRH-like peptides were determined by RIA after trypsin digestion. In human plasma it was observed an N-extended form of TRH-like peptides in substantial concentration. After trypsin and heating, the N-extended forms of TRH-like peptides were rechromatographed on Sephadex G-50. This showed that the TRH-like peptides released have a similar size to TRH. The peptides were then separated by cation exchange chromatography, and the major fraction was unretained, indicating a neutral or acidic nature. Part of the unretained fraction was then chromatographed on anion exchange column in which the major fraction was retained, demonstrating the acidic nature of the peptides. Similar results have been observed in rat and rabbit. The other part of the unretained fraction from cation exchange chromatography of human plasma was purified on HPLC. The results demonstrated that the major component observed by HPLC cochromatographed with synthetic pGlu-Glu-Pro amide. This study represents the first demonstration of a circulating N-extended form of any TRH-like peptide

The causes of cerebral accumulation of amyloid ß-protein (Aß) in most cases of Alzheimer’s disease (AD) remain unknown. We recently found that homozygous deletion of the insulin-degrading enzyme (IDE) gene in mice results in an early and marked elevation of cerebral Aß. Both genetic linkage and allelic association in the IDE region of chromosome 10 have been reported in families with late-onset AD. For IDE to remain a valid candidate gene for late-onset AD on functional grounds, it must be shown that partial loss of function of IDE can still alter Aß degradation, but without causing early, severe elevation of brain Aß. Here, we show that naturally occurring IDE missense mutations in a well-characterized rat model of type 2 diabetes mellitus (DM2) result in decreased catalytic efficiency and a significant 15 to 30% deficit in the degradation of both insulin and Aß. Endogenously secreted Aß40 and Aß42 are significantly elevated in primary neuronal cultures from animals with the IDE mutations, but there is no increase in steady-state levels of rodent Aß in the brain up to age 14 months. We conclude that naturally occurring, partial loss-of-function mutations in IDE sufficient to cause DM2 also impair neuronal regulation of Aß levels, but the brain can apparently compensate for the partial deficit during the life span of the rat. Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD. Farris W., et al. American Journal of Pathology. 2004;164:1425-1434

Schematic diagram of FPP, adenosine and calcitonin interacting with their respective specific receptors to regulate mAC activity and consequent cAMP production in a G protein-mediated manner. Experimental evidence suggests that adenosine receptors and calcitonin receptors regulate different mAC isoforms. Fraser L. R., et al. Molecular Human Reproduction, Vol. 9, No. 12, pp. 739-748, 2003

Mapping of human TCPII gene within 6p21 by FISH on metaphase chromosomes. The dual signal is on band 6p21 (arrows). Ma Y. X., et al. Molecular Human Reproduction, Vol. 8, No. 1, 24-31, January 2002

Multiple tissue Northern blot (Clontech 7759-1) probed with (A) a radiolabelled 681bp TCP11 probe and (B) a ß-actin probe as a control. Sp = spleen; Th = thymus; Pr = prostate; Ts = testis; Ov = ovary; S.I. = small intestine; Co = colon; P.B.L. = peripheral blood leukocytes. Sizes indicated on the left side are in kilobases. Ma Y. X., et al. Molecular Human Reproduction, Vol. 8, No. 1, 24-31, January 2002